diff --git a/.gn b/.gn
index 2a74dea33bd644..f218361a05b55a 100644
--- a/.gn
+++ b/.gn
@@ -8,10 +8,6 @@ import("//third_party/angle/dotfile_settings.gni")
 # The location of the build configuration file.
 buildconfig = "//build/config/BUILDCONFIG.gn"
 
-# The python interpreter to use by default. On Windows, this will look
-# for python3.exe and python3.bat.
-script_executable = "python3"
-
 # These arguments override the default values for items in a declare_args
 # block. "gn args" in turn can override these.
 #
diff --git a/tools/mb/mb.py b/tools/mb/mb.py
index 1ee7fff2cc9232..9275cb07d6451e 100755
--- a/tools/mb/mb.py
+++ b/tools/mb/mb.py
@@ -1087,6 +1087,33 @@ def RunGNGen(self, vals, compute_inputs_for_analyze=False, check=True):
       self.WriteFile(gn_runtime_deps_path, '\n'.join(labels) + '\n')
       cmd.append('--runtime-deps-list-file=%s' % gn_runtime_deps_path)
 
+    # Detect if we are running in a vpython interpreter, and if so force GN to
+    # use the real python interpreter. crbug.com/1049421
+    # This ensures that ninja will only use the real python interpreter and not
+    # vpython, so that any python scripts in the build will only use python
+    # modules vendored into //third_party.
+    # This can be deleted when python 3 becomes the only supported interpreter,
+    # because in python 3 vpython will no longer have its current 'viral'
+    # qualities and will require explicit usage to opt in to.
+    prefix = getattr(sys, "real_prefix", sys.prefix)
+    python_exe = 'python.exe' if self.platform.startswith('win') else 'python'
+    # The value of prefix varies. Sometimes it extends to include the bin/
+    # directory of the python install such that prefix/python is the
+    # interpreter, and other times prefix/bin/python is the interpreter.
+    # Therefore we need to check both. Also, it is safer to check prefix/bin
+    # first because there have been previous installs where prefix/bin/python
+    # was the real binary and prefix/python was actually vpython-native.
+    possible_python_locations = [
+        os.path.join(prefix, 'bin', python_exe),
+        os.path.join(prefix, python_exe),
+    ]
+    for p in possible_python_locations:
+      if os.path.isfile(p):
+        cmd.append('--script-executable=%s' % p)
+        break
+    else:
+      self.Print('python interpreter not under %s' % prefix)
+
     ret, output, _ = self.Run(cmd)
     if ret != 0:
       if self.args.json_output: